Poster 9
Presenter: George Sutphin
Wednesday, 3:00 – 5:00pm

A Multi-Organism Approach to Selecting Strong Candidates for Mammalian Longevity Genes

George L. Sutphin*, Shannon Bean*, Matt Kaeberlein**, Ron Korstanje*
*The Jackson Laboratory, **University of Washington

The search for genetic factors involved aging has identified hundreds of genes for which altered expression is capable of increasing life span in one or more model organisms. As the first pharmacological agents targeting these genes begin to be translated into clinical trials for treatment of age-associated disease, it will be useful to prioritize potential clinical targets from the growing list of candidate aging factors that are likely to influence longevity in mammals. We have devised a candidate-gene approach to combine recent genomic methods in mammals with the powerful genetic tools available in invertebrates to identify evolutionarily conserved longevity genes with a high likelihood of impacting mammalian aging. An initial list of longevity-associated genes was selected based on a meta-analysis of human and mouse genome-wide association studies. Orthologs of each gene were then selected in both Caenorhabditis elegans and Saccharomyces cerevisiae. A screen is currently underway to determine whether RNAi knockdown or deletion of each ortholog increases life span in worms or replicative life span in yeast. In cases where life span extension is observed, knockdown of the ortholog will be combined with knockdown of genes in commonly studied aging pathways to look for epistatic interaction. Interesting candidates will be carried forward for longevity studies in mice. Here we provide a detailed description of our screening strategy and report preliminary results.